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BACKGROUND: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations. METHODS: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization. RESULTS: A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis. CONCLUSIONS: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).
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Isquemia Encefálica , Infarto Cerebral , Procedimentos Endovasculares , AVC Isquêmico , Trombectomia , Humanos , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/cirurgia , Infarto Cerebral/tratamento farmacológico , Infarto Cerebral/cirurgia , China , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/etiologia , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/cirurgia , Estudos Prospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/cirurgia , Trombectomia/efeitos adversos , Trombectomia/métodos , Resultado do TratamentoRESUMO
OBJECTIVES: We investigated whether patients with large infarct and the presence or absence of perfusion mismatch are associated with endovascular treatment benefit. METHODS: This is a post-hoc analysis of the Endovascular Therapy in Anterior Circulation Large Vessel Occlusion with a Large Infarct (ANGEL-ASPECT) randomized trial, which enrolled patients within 24 hours of onset with ASPECTS 3 to 5 or ASPECTS 0 to 2 with an infarct core 70 to 100 ml. Mismatch ratio was defined as time-to-maximum (Tmax) >6 s cerebral volume/ischemic core volume, and mismatch volume was defined as Tmax >6 s volume minus ischemic core volume. We divided patients into mismatch ratio ≥1.2 and mismatch volume ≥10 ml, and mismatch ratio ≥1.8 and mismatch volume ≥15 ml groups. The primary outcome was the 90-day modified Rankin Scale score ordinal distribution. Safety outcomes were symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: There were 425 patients included. In both the mismatch ratio ≥1.2 and mismatch volume ≥10 ml (mismatch+, n = 395; mismatch-, n = 31) and mismatch ratio ≥1.8 and mismatch volume ≥15 ml groups (mismatch+, n = 346; mismatch-, n = 80), better 90-day modified Rankin Scale outcomes were found in the endovascular treatment group compared with the MM group (4 [2-5] vs 4 [3-5], common odds ratio [cOR], 1.9, 95% confidence interval [CI] 1.3-2.7, p = 0.001; 4 [2-5] vs 4 [3-5], cOR, 1.9, 95% CI 1.3-2.8, p = 0.001, respectively), but not in patients without mismatch ratio ≥1.2 and mismatch volume ≥10 ml (5 [3-6] vs 5 [4-6], cOR, 1.2, 95% CI 0.3-4.1, p = 0.83), and mismatch ratio ≥1.8 and mismatch volume ≥15 ml (4 [3-6] vs 5 [3-6], cOR, 1.2, 95% CI 0.6-2.7, p = 0.60). However, no interaction effect was found in both subgroups (p interaction >0.10). CONCLUSION: Endovascular treatment was more efficacious than MM in patients with mismatch profiles, but no treatment effect or interaction was noted in the no mismatch profile patients. However, the small sample size of patients with no mismatch may have underpowered our analysis. A pooled analysis of large core trials stratified by mismatch is warranted. ANN NEUROL 2024.
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BACKGROUND: Stroke etiology could influence the outcomes in patients with basilar-artery occlusion (BAO). This study aimed to evaluate the differences in efficacy and safety of best medical treatment (BMT) plus endovascular treatment (EVT) versus BMT alone in acute BAO across different stroke etiologies. METHODS: The study was a post hoc analysis of the ATTENTION trial (Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion), which was a multicenter, randomized trial at 36 centers in China from February 2021 to September 2022. Patients with acute BAO were classified into 3 groups according to stroke etiology (large-artery atherosclerosis [LAA], cardioembolism, and undetermined cause/other determined cause [UC/ODC]). The primary outcome was a favorable outcome (modified Rankin Scale score of 0-3) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 340 patients with BAO were included, 150 (44.1%) had LAA, 72 (21.2%) had cardioembolism, and 118 (34.7%) had UC/ODC. For patients treated with BMT plus EVT and BMT alone, respectively, the rate of favorable outcome at 90 days was 49.1% and 23.8% in the LAA group (odds ratio, 3.08 [95% CI, 1.38-6.89]); 52.2% and 30.8% in the cardioembolism group (odds ratio, 2.45 [95% CI, 0.89-6.77]); and 37.5% and 17.4% in the UC/ODC group (odds ratio, 2.85 [95% CI, 1.16-7.01]), with P=0.89 for the stroke etiology×treatment interaction. The rate of symptomatic intracranial hemorrhage in EVT-treated patients with LAA, cardioembolism, and UC/ODC was 8.3%, 2.2%, and 3.2%, respectively, and none of the BMT-treated patients. Lower 90-day mortality was observed in patients with EVT compared with BMT alone across 3 etiology groups. CONCLUSIONS: Among patients with acute BAO, EVT compared with BMT alone might be associated with favorable outcomes and lower 90-day mortality, regardless of cardioembolism, LAA, or UC/ODC etiologies. The influence of stroke etiology on the benefit of EVT should be explored by further trials. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04751708.
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Procedimentos Endovasculares , Insuficiência Vertebrobasilar , Humanos , Procedimentos Endovasculares/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Insuficiência Vertebrobasilar/cirurgia , Insuficiência Vertebrobasilar/complicações , Resultado do Tratamento , Acidente Vascular Cerebral/cirurgia , Acidente Vascular Cerebral/etiologia , China/epidemiologiaRESUMO
BACKGROUND: Sex disparities in acute large vessel occlusion (LVO) following endovascular treatment (EVT) have been recently reported. However, there is uncertainty about the effect of sex differences on functional outcomes after EVT, particularly in an Asian population. The present study aimed to compare the clinical and safety outcomes between men and women with anterior circulation LVO treated with EVT. METHODS: We analyzed data from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke: a Prospective Multicenter Registry Study) Registry, which was conducted at 111 hospitals from 26 provinces in China between November 2017 and March 2019. Men and women with anterior circulation LVO treated with EVT were matched using propensity scores. After a 1:1 propensity score matching, we compared the clinical outcomes including 90-day ordinal modified Rankin Scale distribution (primary outcome), procedure duration, successful reperfusion, symptomatic intracranial hemorrhage, and mortality. Furthermore, we explored sex modification on the primary outcome in subgroup analysis. RESULTS: Of 1321 patients, 483 (36.6%) were women and 838 (63.4%) were men. The mean age for women and men were 68 and 62 years old, respectively. Among 578 patients identified after matching, there were no sex differences (men versus women) in 90-day ordinal modified Rankin Scale distribution (median [interquartile range], 4 [1-5] versus 3 [1-5], P=0.464), successful reperfusion (86.5% versus 91.0%, P=0.089), symptomatic intracranial hemorrhage (6.5% versus 7.9%, P=0.512), and mortality within 90 days (17.7% versus 17.0%, P=0.826). However, men had a longer median procedure duration than women (86 [52-128] versus 72 [48-110] minutes, ß=14.51, [95% CI, 4.19-24.84]; P=0.006). Subgroup analysis showed that in patients with National Institutes of Health Stroke Scale score <15, women tended to have a better outcome than men, whereas there was no gender effect in those with National Institutes of Health Stroke Scale score ≥15 (P for interaction=0.032). CONCLUSIONS: Overall, this matched-control study from the ANGEL-ACT study showed similar clinical outcomes between men and women with anterior circulation LVO treated with EVT. However, in the subgroup of patients presenting with lower stroke severity (ie, National Institutes of Health Stroke Scale score <15), women tended to have a better outcome than men highlighting a potential sex disparity for further investigation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03370939.
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Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Isquemia Encefálica/terapia , AVC Isquêmico/etiologia , Estudos Prospectivos , Acidente Vascular Cerebral/terapia , Hemorragias Intracranianas/etiologia , Procedimentos Endovasculares/métodos , Resultado do Tratamento , TrombectomiaRESUMO
PURPOSE: Acute vertebrobasilar artery occlusion (VBAO) is a catastrophic disease for patients. There is evidence that the eventual patient outcome depends on patient-specific and procedural factors. This study aimed to identify the incidence and independent predictors of the 90-day poor outcome in VBAO after endovascular treatment (EVT). METHODS: Subjects were selected from the ANGEL-ACT registry. The 90-day poor outcome was defined as a 90-day modified Rankin Scale (mRS) of 4 to 6. Logistic regression analyses were performed to determine the independent predictors of the 90-day poor outcome. RESULTS: Of the 347 enrolled patients with acute VBAO undergoing EVT, 176 (50.7%) experienced the 90-day poor outcome. Multivariate logistic regression indicated that only the use of general anesthesia (GA) (odds ratio [OR] = 2.04; 95% confidence interval [CI], 1.23-3.37; P = 0.006) and heparin during the procedure (OR =1.74; 95% CI, 1.06-2.86; P = 0.028), admission National Institute of Health Stroke Scale (NIHSS) ≥ 26 (OR=3.96; 95% CI, 2.37-6.61; P < 0.001), and time from onset to puncture (OTP) ≥ 395 min (OR=1.91; 95% CI, 1.14-3.20; P = 0.014) and procedure duration ≥ 102 min (OR = 1.70; 95% CI, 1.04-2.79; P = 0.036) were independent predictors of the 90-day poor outcome after EVT. Furthermore, admission NIHSS (OR > 36 vs. ≤ 11 = 9.01, P for trend < 0.001), OTP (OR > 441min vs. ≤ 210 min = 2.71, P for trend = 0.023), and procedure duration (OR > 145 min vs. ≤ 59 min = 2.77, P for trend = 0.031) were significantly associated with increasing risk of the 90-day poor outcome. CONCLUSIONS: Poor outcome after EVT at 90 days occurred in 50.7% of acute VBAO patients from the ANGEL-ACT registry. Our study found several predictors of the 90-day poor outcome which should be highly considered in daily practice to improve acute VBAO management. CLINICAL TRIAL REGISTRATION : http://www. CLINICALTRIALS: gov . Unique identifier: NCT03370939.
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Arteriopatias Oclusivas , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Anestesia Geral/efeitos adversos , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/cirurgia , Procedimentos Endovasculares/métodos , Sistema de Registros , Acidente Vascular Cerebral/etiologia , Trombectomia , Resultado do TratamentoRESUMO
BACKGROUND: A subgroup of patients with acute large vessel occlusion (ALVO) may experience delayed neurological improvement (DNI) after endovascular treatment (EVT). Our study aimed to investigate the incidence and independent predictors of DNI in patients with ALVO after EVT. METHODS: We selected subjects from ANGEL-ACT Registry. The definition of DNI is patients with ALVO who did not experience early neurological improvement (ENI) despite complete recanalization after EVT. These patients achieved a 90-day favorable outcome assessed by a modified Rankin Scale (mRS) score. We defined ENI as a ≥ 4-point decrease in the National Institutes of Health Stroke Scale (NIHSS) between baseline and 24 h or NIHSS of 0 or 1 at 24 h, with complete recanalization after EVT. We performed logistic regression analyses to determine the independent predictors of DNI. RESULTS: Among the 1056 enrolled patients, 406 (38.4%) did not experience ENI. 106 (26.1%) patients without ENI achieved DNI. On Multivariate analysis, lower admission NIHSS score (odds ratio [OR] = 1.17,95% confidence interval [CI]: 1.11-1.23, P < 0.001), underlying ICAD (OR = 2.03, 95% CI: 1.07-3.85, P = 0.029) and absence of general anesthesia (OR = 2.13, 95% CI: 1.24-3.64, P = 0.006) were independent predictors of DNI. CONCLUSION: DNI occurred in 26.1% of patients with ALVO who did not experience ENI after EVT. Our study identified several independent predictors of DNI that should be highly considered in daily clinical practice to improve ALVO management.
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Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento , Terapia Trombolítica , Procedimentos Endovasculares/efeitos adversos , Sistema de Registros , Isquemia Encefálica/tratamento farmacológico , TrombectomiaRESUMO
BACKGROUND: The role of stroke etiology subtype in patients with acute large vessel occlusion on the occurrence of hemorrhagic transformation (HT) after endovascular treatment is poorly studied, and which factors mediate their relationship remains largely unknown. We utilized nationwide registry data to explore the association of stroke subtype (cardioembolism versus large artery atherosclerosis) with HT and to identify the possible mediators. METHODS: A total of 1015 subjects were selected from the ANGEL-ACT registry (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke)-a prospective consecutive cohort of acute large vessel occlusion patients undergoing endovascular treatment at 111 hospitals in China between November 2017 and March 2019-and divided into large artery atherosclerosis (n=538) and cardioembolism (n=477) according to the Trial of ORG 10172 in Acute Stroke Treatment criteria. The types of HT included any intracerebral hemorrhage (ICH), parenchymal hematoma, and symptomatic ICH within 24 hours after endovascular treatment. The association between stroke subtype and HT was analyzed using a logistic regression model. Mediation analysis was done to assess how much of the effect of stroke subtype on HT was mediated through the identified mediators. RESULTS: Stroke subtype (cardioembolism versus large artery atherosclerosis) was associated with increased risk of any ICH (29.8% versus 16.5%; odds ratio, 2.03 [95% CI, 1.22-3.36]), parenchymal hematoma (14.3% versus 5.4%; odds ratio, 2.90 [95% CI, 1.38-6.13]), and symptomatic ICH (9.9% versus 4.7%; odds ratio, 2.59 [95% CI, 1.09-6.16]) after adjustment for potential confounders. The more thrombectomy passes in cardioembolism patients had a significant mediation effect on the association of stroke subtype with increased risk of HT (any ICH, 15.9%; parenchymal hematoma, 13.4%; symptomatic ICH, 14.2%, respectively). CONCLUSIONS: Stroke subtype is an independent risk factor for HT within 24 hours following endovascular treatment among acute large vessel occlusion patients. Mediation analyses propose that stroke subtype contributes to HT partly through thrombectomy pass, suggesting a possible pathomechanistic link. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03370939.
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Aterosclerose , Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Aterosclerose/complicações , Isquemia Encefálica/terapia , Hemorragia Cerebral/etiologia , Ensaios Clínicos como Assunto , Procedimentos Endovasculares/métodos , Hematoma/complicações , Humanos , Estudos Prospectivos , Sistema de Registros , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/cirurgia , Trombectomia/efeitos adversos , Trombectomia/métodos , Resultado do TratamentoRESUMO
BACKGROUND: In patients undergoing mechanical thrombectomy (MT), adjunctive antithrombotic might improve angiographic reperfusion, reduce the risk of distal emboli and reocclusion but possibly expose patients to a higher intracranial hemorrhage risk. This study evaluated the safety and efficacy of combined MT plus eptifibatide for acute ischemic stroke. METHODS: This was a propensity-matched analysis of data from 2 prospective trials in Chinese populations: the ANGEL-ACT trial (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke) in 111 hospitals between November 2017 and March 2019, and the EPOCH trial (Eptifibatide in Endovascular Treatment of Acute Ischemic Stroke) in 15 hospitals between April 2019 and March 2020. The primary efficacy outcome was good outcome (modified Rankin Scale score 0-2) at 3 months. Secondary efficacy outcomes included the distribution of 3-month modified Rankin Scale scores and poor outcome (modified Rankin Scale score 5-6) and successful recanalization. The safety outcomes included any intracranial hemorrhage, symptomatic intracranial hemorrhage, and 3-month mortality. Mixed-effects logistic regression models were used to account for within-hospital clustering in adjusted analyses. RESULTS: Eighty-one combination arm EPOCH subjects were matched with 81 ANGEL-ACT noneptifibatide patients. Compared with the no eptifibatide group, the eptifibatide group had significantly higher rates of successful recanalization (91.3% versus 81.5%; P=0.043) and 3-month good outcomes (53.1% versus 33.3%; P=0.016). No significant difference was found in the remaining outcome measures between the 2 groups. All outcome measures of propensity score matching were consistent with mixed-effects logistic regression models in the total population. CONCLUSIONS: This matched-control study demonstrated that MT combined with eptifibatide did not raise major safety concerns and showed a trend of better efficacy outcomes compared with MT alone. Overall, eptifibatide shows potential as a periprocedural adjunctive antithrombotic therapy when combined with MT. Further randomized controlled trials of MT plus eptifibatide should be prioritized. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03844594 (EPOCH), NCT03370939 (ANGEL-ACT).
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/cirurgia , Eptifibatida , Humanos , Hemorragias Intracranianas/etiologia , Estudos Prospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Resultado do TratamentoRESUMO
Symptomatic intracranial hemorrhage (SICH) is a catastrophic complication of endovascular treatment (EVT) for large vessel occlusion (LVO). We aimed to investigate the incidence and predictors of SICH after EVT. Patients were selected from the ANGEL-ACT registry. We diagnosed SICH according to the Heidelberg Bleeding Classification. Logistic regression analyses were performed to determine the independent predictors of SICH. Of the 1283 patients, SICH was observed in 116 patients (9.0%). On multivariable analysis, admission National Institutes of Health Stroke Scale (NIHSS) > 12 (odds ratio [OR] = 1.86, 95% confidence interval [CI]: 1.11-3.11, P = 0.018), admission Alberta Stroke Program Early CT Score (ASPECTS) < 6 (OR = 2.98, 95%CI: 1.68-5.29, P < 0.001), general anesthesia (OR = 1.81, 95%CI: 1.20-2.71, P = 0.004), prior intravenous thrombolysis (OR = 1.58, 95%CI: 1.04-2.40, P = 0.031), number of mechanical thrombectomy passes > 2 (OR = 1.68, 95%CI: 1.10-2.57, P = 0.016), and procedure duration > 96 min (OR = 1.82, 95%CI: 1.20-2.77, P = 0.005) were associated with high risk of SICH, whereas SICH was negatively associated with underlying intracranial atherosclerotic disease (OR = 0.45, 95%CI: 0.26-0.79, P = 0.021). The incidence of SICH after EVT for anterior LVO was 9.0% in ANGEL-ACT registry. Our study identified some predictors, which may assist doctors in identifying LVO patients with a high risk of SICH and making the optimal peri-procedural management strategies for such patients.
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Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Isquemia Encefálica/etiologia , Procedimentos Endovasculares/efeitos adversos , Humanos , Hemorragias Intracranianas/diagnóstico , Hemorragias Intracranianas/epidemiologia , Hemorragias Intracranianas/etiologia , Sistema de Registros , Acidente Vascular Cerebral/etiologia , Trombectomia/efeitos adversos , Resultado do TratamentoRESUMO
A recent randomized controlled trial DIRECT-MT (Direct Intra-Arterial Thrombectomy to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals) compared the safety and efficacy of mechanical thrombectomy (MT) versus combined intravenous thrombolysis (IVT) and MT for acute large vessel occlusion. The current study utilized a prospective, nationwide registry to validate the results of the DIRECT-MT trial in a real-world practice setting. Subjects were selected from a prospective cohort of acute large vessel occlusion patients undergoing endovascular treatment at 111 hospitals from 26 provinces in China (ANGEL-ACT registry [Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke]) between November 2017 and March 2019. All patients eligible for IVT and receiving MT were reviewed and then grouped according to whether prior IVT or not (MT and combined IVT+MT). After a 1:1 propensity score matching, the outcome measures including the 90-day modified Rankin Scale, successful recanalization, door-to-puncture time, symptomatic intracranial hemorrhage, and intraprocedural embolization were compared. A total of 1026 patients, 600 in the MT group and 426 in the combined group, were included. Among 788 patients identified after matching, there were no significant differences in the 90-day modified Rankin Scale (median, 3 versus 3 points; P=0.82) and successful recanalization (86.6% versus 89.3%; P=0.23) between the two groups; however, patients of the MT group had a shorter door-to-puncture time (median, 112 versus 136 minutes; ß=−45.02 [95% CI, −68.31 to −21.74]), lower rates of symptomatic intracranial hemorrhage (5.5% versus 10.1%; odds ratio, 0.52 [95% CI, 0.300.91]), and embolization (4.6% versus 8.1%; odds ratio, 0.54 [95% CI, 0.300.98]) than those of the combined group. This matched-control study largely confirmed the findings of the DIRECT-MT trial in a real-world practice setting, suggesting that MT may carry similar effectiveness to combined IVT+MT for acute large vessel occlusion patients, despite MT alone seems to be associated with a shorter in-hospital delay until procedure, lower risks of symptomatic intracranial hemorrhage, and embolization. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939
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Terapia Combinada/métodos , Acidente Vascular Cerebral/terapia , Trombectomia/métodos , Terapia Trombolítica/métodos , Idoso , Estudos de Casos e Controles , Procedimentos Endovasculares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de RegistrosRESUMO
BACKGROUND AND OBJECTIVE: The effect of atrial fibrillation (AF) on outcomes of endovascular treatment (EVT) for acute ischemic stroke (AIS) is controversial. This study aimed to investigate the association of AF with outcomes after EVT in AIS patients. METHODS: Subjects were selected from ANGEL-ACT registry (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke) - a prospective consecutive cohort of AIS patients undergoing EVT at 111 hospitals in China between November 2017 and March 2019, and then grouped according to having a history of AF or not. After 1:1 propensity score matching, the outcome measures including the 90-day modified Rankin Scale (mRS) score, successful recanalization after final attempt, symptomatic intracranial hemorrhage (ICH) within 24 h, and death within 90 days were compared. RESULTS: A total of 1755 patients, 550 with AF and 1205 without AF, were included. Among 407 pairs of patients identified after matching, no significant differences were found in the mRS score (median: 3 vs. 3 points; P = 0.29), successful recanalization (87.2 vs. 85.3%; P = 0.42), symptomatic ICH (9. 4 vs. 9.1%; P = 0.86) and death (16.3 vs. 18.4%; P = 0.44) between patients with and without AF. CONCLUSION: The findings of this matched-control study show comparable outcomes of EVT in Chinese AIS patients with and without AF, which do not support withholding EVT in patients with both AIS and AF. TRIAL REGISTRATION: NCT03370939 First registration date: 28/09/2017 First posted date: 13/12/2017.
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Fibrilação Atrial , Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Isquemia Encefálica/complicações , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/terapia , Humanos , Estudos Prospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Resultado do TratamentoRESUMO
BACKGROUND: The coexistence of chronic diseases among people with stroke is common. However, little is known about the extent of incremental healthcare expenditures associated with having physically and psychologically chronic conditions among stroke survivors. METHODS: We used the nationally representative data from the China Health and Nutrition Survey, including 36,076 participants enrolled as our analytic cohort of ten years of follow-up visits (2006, 2009, 2011, 2015). Chronic conditions include hypertension, diabetes, obesity, and impaired cognitive function. Two-part models were used to estimate the effect of comorbid chronic conditions on total annual healthcare expenditure, out-of-pocket (OOP) healthcare expenditure, and incidence of catastrophic healthcare expenditure (CHE). RESULTS: Among survivors of stroke during 2006 to 2015, the prevalence rates of hypertension, diabetes, obesity and impaired cognitive function were 75.5, 9.8, 12.7 and 65.1%, significantly higher than those among adults without stroke history (27.9, 2.7, 10.0 and 41.2%). Having hypertension ($794.5, p = 0.004), diabetes ($3978.5, p < 0.001) were associated with the largest incremental total healthcare expenditures. Stroke survivors with diagnosed hypertension and diabetes had additional 5.7 (p < 0.001) and 10.4 (p < 0.001) percentage point of CHE rate, respectively. Total healthcare expenditures were $2413.0 (P < 0.001) and $5151.7 (P < 0.001) higher among patients with 2, and ≥ 3 chronic conditions, respectively, than those individuals with no chronic conditions. CONCLUSIONS: Excess expenditures associated with chronic diseases were substantial among stroke survivors. These results highlight the needs for both prevention and better management of multimorbidity among stroke survivors, which in turn may lower the financial burden of treating these concurrent comorbidities.
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Efeitos Psicossociais da Doença , Acidente Vascular Cerebral , Adulto , China/epidemiologia , Gastos em Saúde , Humanos , Estudos Longitudinais , Acidente Vascular Cerebral/epidemiologia , SobreviventesRESUMO
AIMS: In previous studies, numerous differential microRNAs (miRNAs) in cerebral ischemic/reperfusion (I/R) injury were identified using the miRNA microarray analysis. However, the relationship between miRNA and cerebral I/R injury remains largely unknown. In this study, we investigated the function and explored the possible mechanism of miR-224-3p in cerebral I/R injury. METHODS: Oxygen glucose deprivation model in N2a cells were used to perform the cerebral I/R injury in vitro. Trypan blue staining, reactive oxygen species (ROS) production, and caspase-3 were measured to evaluate the function of miR-224-3p. RESULTS: Overexpression of miR-224-3p alleviated the apoptosis induced by oxygen glucose deprivation (OGD) and cleaved caspase-3 was significantly reduced. We further provided the possible mechanism that miR-224-3p may protect cells from cerebral I/R injury by targeting FAK family-interacting protein (FIP200). Further rescue experiment proved that overexpression of FIP200 partially blocked the effect of miR-224-3p. CONCLUSIONS: We evaluated the function and mechanism of miR-224-3p in ischemic brain injury. miR-224-3p may serve as a potential target for new therapeutic intervention.
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Apoptose/genética , Proteínas Relacionadas à Autofagia/genética , MicroRNAs/genética , Neurônios/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proteínas Relacionadas à Autofagia/metabolismo , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Caspase 3/genética , Caspase 3/metabolismo , Hipóxia Celular/genética , Linhagem Celular Tumoral , Regulação da Expressão Gênica , Vetores Genéticos , Glucose/deficiência , Glucose/farmacologia , Camundongos , MicroRNAs/agonistas , MicroRNAs/metabolismo , Modelos Biológicos , Mimetismo Molecular , Neurônios/efeitos dos fármacos , Neurônios/patologia , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Oxigênio/farmacologia , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais , TransfecçãoRESUMO
BACKGROUND: Collagen VI-related myopathies are a spectrum of muscular diseases with features of muscle weakness and atrophy, multiple contractures of joints, distal hyperextensibility, severe respiratory dysfunction and cutaneous alterations, attributable to mutations in the COL6A1, COL6A2, and COL6A3 genes. However, no case of collagen VI mutations with hematuria has been reported. We report a 14-year-old boy who had both Bethlem myopathy and recurrent hematuria and who carried a known de novo COL6A1 missense mutation c.877G > A (p.G293R). CASE PRESENTATION: The patient was a 14-year-old boy presenting with muscle weakness from 3 years of age without any family history. Six months before admission, he developed recurrent gross hematuria, three bouts in total, with the presence of blood clots in the urine. Next-generation sequencing of his whole-exome was performed. The result of sequencing revealed a de novo heterozygous G-to-A nucleotide substitution at position 877 in exon 10 of the COL6A1 gene. After treatment, the hematuria healed, but the muscle weakness failed to improve. CONCLUSIONS: Hematuria in Bethlem myopathy can be caused by COL6 mutations, which may be related to the aberrant connection between collagen VI and collagen IV.
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Colágeno Tipo VI/genética , Contratura/genética , Distrofias Musculares/congênito , Adolescente , Contratura/complicações , Contratura/diagnóstico , Contratura/patologia , Hematúria/etiologia , Hematúria/genética , Humanos , Masculino , Distrofias Musculares/complicações , Distrofias Musculares/diagnóstico , Distrofias Musculares/genética , Distrofias Musculares/patologia , Mutação , RecidivaRESUMO
BACKGROUND: Primary familial brain calcification (PFBC) is a rare disorder characterized by distinctive bilateral brain calcification and variable clinical presentations. However, cerebrovascular attack was rarely reported in PFBC patients. We here reported a SLC20A2 mutation patient presenting with acute ischemic stroke. CASE PRESENTATION: A 56 years old man was transferred to our hospital because of 6 days of melena and 3 days of somnolence, agitation and mood changes. Computed tomography (CT) scan showed symmetrical calcifications in bilateral basal ganglia, caudate nucleus, thalami, subcortical white matter and cerebellum, which is consistent with PFBC. Brain magnetic resonance imaging (MRI) revealed acute ischemic stroke in bilateral basal ganglia and periventricular regions. Mutational analysis identified a SLC20A2 gene mutation c.344C > T (p.Thr115Met) in exon 3. One of his daughters had also suffered from brain calcification. MR perfusion imaging revealed hypoperfusion in bilateral basal ganglia, prefrontal and temporal lobe. After treatment, he discharged with a favorable functional outcome but cognitive impairment. CONCLUSIONS: Ischemic stroke can occur in PFBC patients, which may be associated with hypoperfusion and calcification of arteries. And hypoperfusion in frontotemporal lobar may be related with their cognitive impairment.
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Isquemia Encefálica/genética , Calcinose/patologia , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/genética , Acidente Vascular Cerebral/genética , Gânglios da Base/patologia , Análise Mutacional de DNA , Éxons , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Tomografia Computadorizada por Raios XRESUMO
Importance: Endovascular therapy (EVT) demonstrated better outcomes compared with medical management in recent randomized clinical trials (RCTs) of patients with large infarct. Objective: To compare outcomes of EVT vs medical management across different strata of the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and infarct core volume in patients with large infarct. Design, Setting, and Participants: This prespecified secondary analysis of subgroups of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core (ANGEL-ASPECT) RCT included patients from 46 stroke centers across China between October 2, 2020, and May 18, 2022. Participants were enrolled within 24 hours of symptom onset and had ASPECTS of 3 to 5 or 0 to 2 and infarct core volume of 70 to 100 mL. Patients were divided into 3 groups: ASPECTS of 3 to 5 with infarct core volume less than 70 mL, ASPECTS of 3 to 5 with infarct core volume of 70 mL or greater, and ASPECTS of 0 to 2. Interventions: Endovascular therapy or medical management. Main Outcomes and Measures: The primary outcome was the ordinal 90-day modified Rankin Scale (mRS) score. Results: There were 455 patients in the trial; median age was 68 years (IQR, 60-73 years), and 279 (61.3%) were male. The treatment effect did not vary significantly across the 3 baseline imaging subgroups (P = .95 for interaction). The generalized odds ratio for the shift in the 90-day mRS distribution toward better outcomes with EVT vs medical management was 1.40 (95% CI, 1.06-1.85; P = .01) in patients with ASPECTS of 3 to 5 and infarct core volume less than 70 mL, 1.22 (95% CI, 0.81-1.83; P = .23) in patients with ASPECTS of 3 to 5 and infarct core volume of 70 mL or greater, and 1.59 (95% CI, 0.89-2.86; P = .09) in patients with ASPECTS of 0 to 2. Conclusions and Relevance: In this study, no significant interaction was found between baseline imaging status and the benefit of EVT compared with medical management in patients with large infarct core volume. However, estimates within subgroups were underpowered. A pooled analysis of large core trials stratified by ASPECTS and infarct core volume strata is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT04551664.
Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Masculino , Humanos , Idoso , Feminino , Isquemia Encefálica/terapia , Alberta , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/etiologia , Tomografia Computadorizada por Raios X/métodos , Trombectomia/métodos , Infarto/etiologia , Procedimentos Endovasculares/métodos , Resultado do TratamentoRESUMO
Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3-5 or infarct core volume 70-100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18-2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06-2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].
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Background and purpose: Adjunctive tirofiban administration in patients undergoing endovascular treatment (EVT) for acute large vessel occlusion (LVO) has been investigated in several studies. However, the findings are conflict. This study aimed to compare the effect of different administration pathways of tirofiban on patients undergoing EVT for acute LVO with intracranial atherosclerotic disease (ICAD). Methods: Patients were selected from the ANGEL-ACT Registry (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke: A Prospective Multicenter Registry Study) and divided into four groups: intra-arterial (IA), intravenous (IV), and intra-arterial plus intravenous (IA+IV) and non-tirofiban. The primary outcome was 90-day ordinal modified Rankin Scale (mRS) score, and the secondary outcomes included the rates of mRS 0-1, 0-2, and 0-3 at 90-day, successful recanalization. The safety outcomes were symptomatic intracranial hemorrhage (sICH) and other safety endpoints. The multivariable logistic regression models adjusting for potential baseline confounders were performed to compare the outcomes. A propensity score matching (PSM) with a 1:1:1:1 ratio was conducted among four groups, and the outcomes were then compared in the post-matched population. Results: A total of 502 patients were included, 80 of which were in the IA-tirofiban group, 73 in IV-tirofiban, 181 in (IA+IV)-tirofiban group, and 168 in the non-tirofiban group. The median (IQR) 90-day mRS score in the four groups of IA, IV, IA+IV, and non-tirofiban was, respectively 3(0-5) vs. 1(0-4) vs. 1(0-4) vs. 3(0-5). The adjusted common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.77 (95% CI, 0.45-1.30, P = 0.330), with IV-tirofiban vs. non-tirofiban was 1.36 (95% CI, 0.78-2.36, P = 0.276), and with (IA+IV)-tirofiban vs. non-tirofiban was 1.03 (95% CI, 0.64-1.64, P = 0.912). The adjusted OR for mRS 0-1 and mRS 0-2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.51 (95% CI, 0.27-0.98, P = 0.042) and 0.50 (95% CI, 0.26-0.94, P = 0.033). The other outcomes of each group were similar with non-tirofiban group, all P was >0.05. After PSM, the common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.41 (95% CI, 0.18-0.94, P = 0.036), and the OR for mRS 0-1 and mRS 0-2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.28 (95% CI, 0.11-0.74, P = 0.011) and 0.25 (95% CI, 0.09-0.67, P = 0.006). Conclusions: Intra-arterial administration of tirofiban was associated with worse outcome than non-tirofiban, which suggested that intra-arterial tirofiban had a harmful effect on patients undergoing EVT for ICAD-LVO. Clinical trial registration: http://www.clinicaltrials.gov, Unique identifier: NCT03370939.
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PURPOSE: The outcomes of patients with large ischemic core who fail to recanalize with endovascular therapy (EVT) compared to medical management (MM) are uncertain. The objective was to evaluate the clinical and safety outcomes of patients who underwent EVT in patients with large ischemic core and unsuccessful recanalization. METHODS: This was a post hoc analysis of the ANGEL-ASPECT randomized trial. Unsuccessful recanalization was defined as patients who underwent EVT with eTICI 0-2a. The primary endpoint was 90-day very poor outcome (mRS 5-6). Multivariable logistic regression was conducted controlling for ASPECTS, occlusion location, intravenous thrombolysis, and time to treatment. RESULTS: Of 455 patients 225 were treated with MM. Of 230 treated with EVT, 43 (19%) patients had unsuccessful recanalization. There was no difference in 90-day very poor outcomes (39.5% vs. 40%, aOR 0.93, 95% confidence interval, CI 0.47-1.85, pâ¯= 0.95), sICH (7.0% vs. 2.7%, aOR 2.81, 95% CI 0.6-13.29, pâ¯= 0.19), or mortality (30% vs. 20%, aOR 1.65, 95% CI 0.89-3.06, pâ¯= 0.11) between the unsuccessful EVT and MM groups, respectively. There were higher rates of ICH (55.8% vs. 17.3%, pâ¯< 0.001), infarct core volume growth (142.7â¯ml vs. 90.5â¯ml, ßâ¯= 47.77, 95% CI 20.97-74.57â¯ml, pâ¯< 0.001), and decompressive craniectomy (18.6% vs. 3.6%, pâ¯< 0.001) in the unsuccessful EVT versus MM groups. CONCLUSION: In a randomized trial of patients with large ischemic core undergoing EVT with unsuccessful recanalization, there was no difference in very poor outcomes, sICH or death versus medically managed patients. In the unsuccessful EVT group, there were higher rates of any ICH, volume of infarct core growth, and decompressive craniectomy.